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A kind of crystal form conversion method of clarithromycin

A technology of clarithromycin and conversion method, which is applied in the field of clarithromycin crystal form conversion, can solve the problems of product loss and large amount of solvents, and achieve the effect of low cost and high efficiency

Active Publication Date: 2015-12-23
ZHEJIANG GUOBANG PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The crystallization process requires a large amount of solvent and causes a large loss of product

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0015] step 1: Add 20.0 g (0.0267 mol) of crude clarithromycin and 280 ml of ethanol into a 500 ml four-neck reaction flask equipped with a stirrer and a thermometer, and heat up until the solution becomes clear. After the solution was clarified, the stirring speed was reduced, cooled naturally to room temperature, and then frozen at -10°C for 6h.

[0016] Step 2: The frozen solution is filtered to obtain a clarithromycin wet product, and the crystal form of the wet product is O crystal form. The clarithromycin wet product obtained was rinsed with 500 ml of purified water at room temperature (20° C.), and the crystal form of the wet product was Form II. The yield after drying was 19.6g, and the yield was 98.0%. The X powder diffraction pattern of clarithromycin O crystal form is: 4.599 + 0.2, 6.501 + 0.2, 7.621 + 0.2, 9.196 + 0.2, 10.320 + 0.2, 11.021 + 0.2, 11.763 + 0.2, 11.982 + 0.2, 12.398 + 0.2, 12.638 + 0.2, 13.799 + 0.2, 14.941 + 0.2, 17.098 + 0.2, 18.3...

Embodiment 2

[0018] step 1: It is the same as Step 1 of Embodiment 1.

[0019] Step 2: The frozen solution is filtered to obtain a clarithromycin wet product, and the crystal form of the wet product is O crystal form. The obtained clarithromycin wet product was rinsed with 1000 ml of purified water at room temperature (20° C.). The crystal form of the wet product was Form II, and the yield after drying was 19.5 g, a yield of 97.5%.

Embodiment 3

[0021] step 1: It is the same as Step 1 of Embodiment 1.

[0022] Step 2: The frozen solution is filtered to obtain a clarithromycin wet product, and the crystal form of the wet product is O crystal form. The obtained clarithromycin wet product was rinsed with 200 ml of purified water at 50° C., and the crystal form of the wet product was Form II. The yield after drying was 19.7g, and the yield was 98.5%.

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PUM

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Abstract

The invention mainly discloses a crystal form conversion method of clarithromycin, which can convert type O clarithromycin into type II clarithromycin by rinsing wet clarithromycin in water at different temperatures. The present invention can simply and effectively convert clarithromycin from crystal form O to crystal form II by rinsing wet clarithromycin with water, with low cost, high efficiency and almost no loss.

Description

technical field [0001] The invention relates to the conversion of clarithromycin crystal forms in the process of synthesizing clarithromycin, and belongs to the technical field of macrolide drug crystal forms and conversion thereof. Background technique [0002] Clarithromycin (CAM for short), chemical name (-)-2R, 3S, 4S, 5R, 6R, 8R, 10R, 11R, 12S, 13R–3-[(2,6-dideoxy-3- C-methyl-3-O-methyl-α-L-ribopyranosyl)oxy]-13-ethyl-11,12-dihydroxy-6-methoxy-2,4,6,8, 10,12-Hexamethyl{[(3,4,6-trideoxy-3-dimethylamino)-β-D-xylopyranosyl]oxy}-14-oxycyclotetradecane-1, 9-diketone; (-)-2R, 3S, 4S, 5R, 6R, 8R, 10R, 11R, 12S, 13R-3-[(2,6-Dideoxy-3-C-methyl-3-0-methyl -α-L-ribo-hexopyranosyl)-oxy]-13-ethyl-11,12-dihydroxy-6-methoxy-2,4,6,8,10,12-hexamethyl{[(3,4,6-trideoxy -3-dimethylamino)-β-D-xy-lo-hexopyranosyl]oxy}-14-oxacyclotetradecane-1,9-dione; discovered by Taisho Pharmaceutical Co. Ltd. in Japan in 1980, and later by the United States Abbott Laboratories (Abbott Laboratories) su...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07H17/08C07H1/06
Inventor 金勇徐斌侯仲轲王兆刚潘伯安邱家军
Owner ZHEJIANG GUOBANG PHARMA